Pulmonary mechanical and immunologic dysfunction in a murine model
of aids.
Hartsfield, Cynthia L., David Lipke, Yih-Loong Lai, Donald A. Cohen,
and Mark N. Gillespie.
University of Kentucky A.B. Chandler Medical Center, College of
Pharmacy, Division of Pharmacology and Experimental Therapeutics, and
College of Medicine, Department of Microbiology and Immunology,
Lexington, KY 40536-0082
APStracts 3:0235L, 1996.
HIV-infected patients occasionally exhibit alveolar septal wall
thickening and decreases in gas diffusion capacity, but the mechanism
underlying these abnormalities is unknown. The present study
evaluated septal wall thickness and gas exchange properties in a
murine model of the acquired immunodeficiency syndrome (MAIDS) and
determined whether there were alterations in lung lymphocyte
deposition and activation which could contribute to changes in
respiratory structure and function. While alveolar septal wall
thickness did not differ from control at 1, 2, and 4 weeks post
immunosuppressive virus infection, at 8 weeks after infection septal
wall thickness was substantially increased. Immunohistochemical
evaluation at this time revealed marked increases in the septal wall
deposition of fibronectin and collagen type IV. Pulmonary function
tests on anesthetized mice with virus-induced septal wall thickening
demonstrated that while total lung capacity, compliance, and
functional residual capacity were unaltered, diffusion capacity for
carbon monoxide was significantly impaired. A diffuse nonspecific
interstitial pneumonitis was present in lungs of immunodeficient mice
and flow cytometry indicated that both lymphocytes and macrophages
were activated. RT-PCR analysis of lung lymphocytes demonstrated
enhanced mRNA expression for several cytokines known to affect lung
structure. These results show that impaired gas exchange occurs in a
murine model of AIDS and suggest that such alterations may be
mediated by elaboration of cytokines from activated lung lymphocytes
and macrophages.
Received 27 February 1996; accepted in final form 25 November
1996.
APS Manuscript Number L70-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996